Disease progressions

In general, the clinical picture of any LSD is characterized by a progressive course of disease. This reflects the ongoing pathological storage of substrates in particular sites of the body and the subsequent disease processes and progression triggered by that.

One way of following disease progression goes from cells to tissues and organs and from subclinical signs to symptoms to complications. For example, in Gaucher disease type I, the lysosomal substrate storage is almost conclusively confined to tissue macrophages. Subsequently, these macrophages accumulate in the spleen, liver, bone marrow, and sometimes lungs, and trigger a variety of disease processes in these organs. In clinical terms, this then can lead to a variety of subclinical signs (e.g. loss of bone marrow fat fraction), clinical symptoms (e.g. bone pain), and, possibly, complications (e.g. pathological fractures).

Another way of assessing disease progression is based on analyzing the levels of disease processes that can be found within a disease, a patient with that disease, and even different organs within such patient. Such analysis can help determining the assessment or monitoring of patients as well as help choosing therapeutic modalities.

Primary processes (at the cellular level)

Lysosomal storage leading to:

Lysosomal dysfunction and damage

Cellular dysfunction, damage, and/or death

Secondary processes (at the tissue level)

Tissue responses to cellular signals, dysfunction or damage

Such responses might be reversible as well as irreversible

Tertiary processes (lysosome-independent)

Disease processes triggered by (often) irreversible events (which happened either acute or accumulated over time)

For example, in Fabry disease for the kidney (a) and heart (b) this can translate into:

Primary processes

Substrate storage in various renal cells

Storage in cardiomyocytes

Secondary processes

Proteinuria

Left ventricular hypertrophy

Tertiary processes

Uremia-related and other processes triggered by end-stage renal disease

Heart failure triggered by endocardial fibroelastosis